反应详情

温度

95 °C

To a mixture of (S)-3-{(5-bromo-pyrimidin-2-yl)-[3-chloro-5-(trifluoromethyl)benzyl]-amino}-pyrrolidine-1-carboxylic acid isopropyl ester (0.19 mmol, 100 mg), 1-methylpyrazol-3-yl-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (0.23 mmol, 48 mg), tetrakis(triphenylphosphine)palladium(0) (0.02 mmol, 22 mg) and 2M aqueous sodium hydrogen carbonate (0.19 mL) in 1,2-dimethoxy-ethane (0.6 mL) is allowed to warm to 95° C. and stirred for 3 hours. The mixture is cooled to room temperature and then added water. The mixture is extracted with CH2Cl2. The combined organic layer is dried over Na2SO4, filtrated, and concentrated under reduced pressure. The obtained residue is purified by silica gel column chromatography (eluent: CH2Cl2/EtOAc). To the obtained mixture in CH2Cl2 (1 mL) is added saturated aqueous sodium carbonate (0.04 mL) and NaIO4 (82 mg). The mixture is stirred at room temperature for 3 hours. The mixture is concentrated under reduced pressure. The obtained residue is purified by silica gel column chromatography (eluent: n-hexane/EtOAc) to give (S)-3-{(3-Chloro-5-trifluoromethyl-benzyl)-[5-(1-methyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amino}-pyrrolidine-1-carboxylic acid isopropyl ester (67 mg, 67%); ESI-MS m/z: 523 [M+1]+, Retention time 2.16 min (condition A).

1. temperatureThe mixture is cooled to room temperature
2. extractionThe mixture is extracted with CH2Cl2
3. dry with materialThe combined organic layer is dried over Na2SO4
4. filtrationfiltrated
5. concentrationconcentrated under reduced pressure
6. customThe obtained residue is purified by silica gel column chromatography (eluent: CH2Cl2/EtOAc)
7. additionTo the obtained mixture in CH2Cl2 (1 mL) is added saturated aqueous sodium carbonate (0.04 mL) and NaIO4 (82 mg)
8. stirringThe mixture is stirred at room temperature for 3 hours
9. concentrationThe mixture is concentrated under reduced pressure
10. customThe obtained residue is purified by silica gel column chromatography (eluent: n-hexane/EtOAc)